An amendment to this paper has been published and can be accessed via the original article.The synergistic effect of radiotherapy (RT) in combination with immunotherapy has been shown in several clinical trials and case reports. The overlapping pulmonary toxicity induced by thoracic RT and programmed death 1/programmed death ligand-1 (PD-1/PD-L1) blockades is an important issue of clinical investigation in combination treatment. Thus far, the underlying mechanism of this toxicity remains largely unknown.
In this review, we discuss the unique pattern of radiation recall pneumonitis (RRP) induced by PD-1 blockade. The clinical presentation is different from common radiation pneumonitis (RP) or RRP induced by cytotoxic drugs. The immune checkpoint inhibitors may evoke an inflammatory reaction in patients' previously irradiated fields, with infiltrating lymphocytes and potential involvement of related cytokines. All RRP patients have showed durable response to anti-PD-1/PD-L1. RRP is manageable; however, interruption of checkpoint blockades is necessary and immunosuppressive treatment should be started immediately. Further analyses of the predictive factors, including RT dosimetric parameters, tumor-infiltrating lymphocytes (TILs), and PD-L1 expression, are needed given the wide use of immune checkpoint inhibitors and high mortality from lung toxicity with the combination treatment.
Immune checkpoint inhibitors may evoke an RRP in the patients' previously irradiated fields. Interactions between immune checkpoint inhibitors and radiotherapy should be studied further.
Immune checkpoint inhibitors may evoke an RRP in the patients' previously irradiated fields. Interactions between immune checkpoint inhibitors and radiotherapy should be studied further.Adults with a low socioeconomic position (SEP) are more likely to engage in unhealthy diets as compared to adults with high SEP. However, individual-level educational interventions aiming to improve food choices have shown limited effectiveness in adults with low SEP. Environmental-level interventions such as nudging strategies however, may be more likely to benefit low SEP groups. We aimed to review the evidence for the effectiveness of nudges as classified according to interventions in proximal physical micro-environments typology (TIPPME) to promote healthy purchases, food choice, or affecting energy intake or content of purchases, within real-life food purchasing environments. Second, we aimed to investigate the potentially moderating role of SEP.
We systematically searched PubMed, EMBASE, and PsycINFO until 31 January 2018. Studies were considered eligible for inclusion when they i) complied with TIPPME intervention definitions; ii) studied actual purchases, food choice, or energy intake or content obute to improving population dietary behaviours. Evidence investigating the moderating role of SEP was limited, although some studies reported greater effects in low SEP subgroups. We conclude that more high-quality studies obtaining detailed data on participant's SEP are needed.
This systematic review is registered in the PROSPERO database ( CRD42018086983 ).
This systematic review is registered in the PROSPERO database ( CRD42018086983 ).The translation of biomedical research discoveries into clinical practice is marked by extended timelines (averaging 17?years) and multiple sequential process steps. However, even after a drug, device, diagnostic tool or unique therapeutic procedure successfully navigates through clinical testing to approval, real barriers remain in applying and scaling the innovation in practice.
Mayo Clinic initiated the Transform the Practice programme to facilitate multidisciplinary team and convergence science to continuously reinvent solutions to address unmet patient needs and accelerate the application of next-generation healthcare solutions. During a 5-year period, 24 programme teams received financial resources, barrier-removing engagement from clinical and research leadership, and enhanced administrative support, including dedicated project managers.
The approach created value in facilitating consistent progress toward project objectives and resulted in multiple publications, new extramural funding sources, and implementation of new tests and services into the clinical practice. This report describes the concentrated institutional effort to accelerate the discovery-translation-application continuum in an academic medical centre and highlights successful applications and persistent obstacles.
The Transform the Practice approach is effective in moving high-potential research discoveries closer to implementation in the clinical practice. Its concepts, including the application of structured project management methodology, may be quickly integrated to shorten an organisation's time to implementing its most important discoveries.
The Transform the Practice approach is effective in moving high-potential research discoveries closer to implementation in the clinical practice. Its concepts, including the application of structured project management methodology, may be quickly integrated to shorten an organisation's time to implementing its most important discoveries.Elevated blood homocysteine levels, termed hyperhomocysteinemia (HHcy), is a prevalent risk factor for Alzheimer's disease (AD) in elderly populations. While dietary supplementation of B-vitamins is a generally effective method to lower homocysteine levels, there is little if any benefit to cognition. https://www.selleckchem.com/products/OSI-906.html In the context of amyloid pathology, dietary-induced HHcy is known to enhance amyloid deposition and certain inflammatory responses. Little is known, however, about whether there is a more specific effect on microglia resulting from combined amyloid and HHcy pathologies.
The present study used a knock-in mouse model of amyloidosis, aged to 12?months, given 8?weeks of B-vitamin deficiency-induced HHcy to better understand how microglia are affected in this comorbidity context.
We found that HHcy-inducing diet increased amyloid plaque burden, altered the neuroinflammatory milieu, and upregulated the expression of multiple damage-associated and "homeostatic" microglial genes.
Taken together, these data indicate complex effects of comorbid pathologies on microglial function that are not driven solely by increased amyloid burden.